Tumour growth

Since COX-2 is overexpressed in tumour cells, such as those of colorectal cancer, it was anticipated that selective COX-2 inhibitors may inhibit tumour growth. 

ET-1 also stimulates anti-apoptotic signal cascades in fibroblasts, vascular smooth muscles and endothelial cells (via phosphatidylinositol-3-kinase and Akt/pro-tein kinase B). In prostate and ovarian cancer, upregulation of endothelin synthesis and ETA receptors has been associated with a progression of the disease. The inhibiton of ETA receptors results in a reduced tumour growth. In malignant melanoma, ETB receptors are associated with tumour progression. Endothelins can also stimulate apoptosis in stretch-activated vessels via the ETB receptor, which contrasts the above-mentioned effects. The molecular basis for these differential anti- and pro-apoptotic reactions mediated by endothelins remains elusive. 

PRYME I F, PUSZTAI A, BARDOCZ s, EWEN s w (1998) The indnction of gut hyperplasia by ph)dohaemagglutinin in the diet and limitation of tumour growth. Histol Histopathol. 13 575-83. 

Patel, J. B., J. Mehta et al. (2007). Novel retinoic acid metabolism blocking agents have potent inhibitory activities on human breast cancer cells and tumour growth. Br. J. Cancer 96(8) 1204—1215. 

The antibody brings about its effect by inhibiting angiogenesis (the formation of new blood vessels), a process required to support tumour growth. Specifically, the antibody binds human vascular endothelial growth factor. This prevents the latter from binding to its cell surface receptor, a process central to triggering new blood vessel formation in both normal and diseased tissue. 

F8. Fotsis, T., Zhang, T., Pepper, M. S., Adlercreutz, H., Montesano, R., Nawroth, P. P., and Schwergerer, L., The endogenous oestrogen metabolite 2-methoxyoestradiol inhibits angiogenesis and suppresses tumour growth. Nature (London) 368, 237-239 (1994). 

Nagata, H., Kikuchi, Y., Tode, T., Hirata, J., Kita, T., Ishii, K., Kudoh, K., Nagata, I., and Shinomiya, N. (1998). Inhibitory effects of ginsenoside Rh-2 on tumour growth in nude mice bearing human ovarian cancer cells. ]pn. J. Cancer Res. 89, 733-740. 

Urano, T., et al., Efp targets 14-3-3 sigma for proteolysis and promotes breast tumour growth. Nature, 2002, 417(6891), 871-5. 

Garkavtsev I, Kozin SV, Chernova O, Xu L, Winkler F, Brown E, Barnett GH, Jain RK (2004) The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis. Nature 428 328-332... 

Research is currently directed towards a better understanding of the metabolic alterations of cancer patients, the definition of nutritional regimens that can efficiently support the host without promoting tumour growth, and on the impact of nutritional pharmacology on the host-tumour relationship. Glutamine, arginine, ornithine-... 

At the simplest level, the successful delivery of cytotoxic agents, either as small molecules or associated with polymers or liposomes, to a soUd tumour depends on the relationship between the tumour cells and the blood vessels supporting their growth. Therefore the first requirement for effective delivery is a fully functional vasculature with respect to perfusion function. For those strategies of treatment where blockade of the tumour blood flow or inhibition of tumour growth is associated with angiogenesis, other considerations need to be taken into account as will be discussed in Chapter 9. 

Other limitations of mouse/rat models are that tumour growth is different in the animal model compared to the situation in man.Tumour growth is more rapid in the rat/mouse model which has an effect on vascularization and intra-tumoural pressure for example. These factors can, as discussed in Section 8.4, have great impact on tumour penetration and uptake of the MAb-based drug-targeting constructs. 

Molecular Control of Tumour Growth-related Angiogenesis... 

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